Adjustments in the rates of renal sodium and water excretion constitute the major defense of man's extracellular fluid volume against potentially disruptive effects of variations in the intake and extrarenal loss of these substances. Likewise, the modulation of the rate at which filtered bicarbonate is reabsorbed by the kidney is critically important in regulating the acid-base balance of the body. This research program is aimed at clarifying our understanding of solute and water transport mechanisms, operating at the level of individual renal tubules and capillaries, that underly these homeostatic adjustments. Clearance and micropuncture techniques will be used to examine experimentally induced variations in solute and water transport in the rat kidney. The data obtained in these studies will be interpreted within the framework of quantitative models designed to extract values of the membrane transport parameters which most clearly characterize the process under consideration. Specifically, these studies will (a) assess the quantitative effects of molecular charge on the glomerular filtration of macromolecules, in relation to proteinuria, (b) develop and refine mathematical models of the urinary acidification process suitable for use in characterizing the transepithelial movement of bicarbonate and carbon dioxide, and explaining the high intrarenal partial pressure of carbon dioxide, and (c) investigate the dynamics of solute and water transport across the vasa recta, in relation to urinary concentration.